https://scholars.lib.ntu.edu.tw/handle/123456789/193428
標題: | 以活體試驗探討YC-1(一種能刺激soluble guanylate cyclase的藥物)對白兔陰莖勃起的影響 | 作者: | 劉詩彬 | 關鍵字: | YC-1, soluble guanylate cyclase, phosphodiesterase | 公開日期: | 2001 | 出版社: | 臺北市:國立臺灣大學醫學院泌尿科 | 摘要: | Objective In the previous study, the effects of YC-1, a novel nitric oxide (NO) independent soluble guanylate cyclase (sGC) stimulator on isolated rabbit cavernous tissue had been investigated. The results showed YC-1 induced cavernous smooth muscle relaxation and enhanced the relaxant effects of nitroprusside. The mechanisms of the effects are through sGC stimulation and possibly phospodiesterase (PDE) inhibition. The current study was designed to perform in vivo evaluation of the effects of YC-1 on rabbit penile erection. Mater ials and methods Mature male New Zealand White rabbits were used in this study. The right external carotid artery was cannulated for continuous blood pressure monitoring. Two 25-gauge butterfly needles were inserted into each corpus cavernosum for intracavernous injection of drugs and intracavernous pressure measurement. Increasing doses of YC-1, papaverine and prostaglandin E1 were injected into the corpus cavernosum and the change of intracavernous pressure was detected and recorded. The dose-response curve of each drug was then achieved. After pretreatment of a low dose of YC-1 for 20 minutes, the dose-response curves of papaverine and prostaglandin E1 were determined again. Results 1) Intracavernous YC-1 injection increased the intracavernous pressue of the rabbits’ penises in a dose-dependent manner but to only mild to moderate extent. 2) 3 Intracavernous PGE1 injection increased the intracavernous pressue of the rabbits’ penises mildly and the effects were enhanced by the pretreatment of YC-1. 3) Intracavernous papaverine injection significantly and remarkably increased the intracavernous pressue of the rabbits’ penises in a dose-dependent manner. With the pretreatment of a low dose of YC-1, intracavernous pressure of the rabbits increased significantly more and the dose-response curve was shifted to the left. Conclusions Intracavernous YC-1 injection increased the intracavernous pressue of the rabbits’ penises mildly to moderately resulting in penile tumescence. Intracavernous papaverine injection increased the intracavernous pressue of the rabbits’ penises significantly and remarkably resulting in fully rigid penile erection and its effect was enhanced by the pretreatment of YC-1. 研究目的: YC-1 是國內自行研發出的一種不需經由NO 作用即可刺激soluble guanylate cyclase 使得細胞內cGMP 增加的新藥物。我們在88 年度國科會專題 計畫“一種不經NO 誘導即能刺激的藥物YC-1 對白兔陰莖海綿體平滑肌的影響” 中,發現YC-1 能使phenylephrine precontracted 白兔cavernous strips 產生 dose-dependent 的放鬆,且其放鬆效果會被sGC inhibitor ODQ 所抑制;YC-1 也能明顯地加強sodium nitroprusside 的放鬆效果。進一步的實驗則証明YC-1 會使白兔陰莖海綿體平滑肌內的cGMP 明顯地增加。體外試驗的具體結果引發了 我們進行活體試驗的動機。 研究對象與方法:我們將使用性成熟的雄性紐西蘭白兔(體重約3 至4 公斤)進 行實驗。在麻醉後把一支polyethylene catheter (PE60)放置於external carotid artery 來監視血壓;將白兔陰莖皮膚切開後,把兩支25 號蝴蝶針插入 白兔陰莖海綿體內,一支用以進行海綿體內藥物注射,另一支則連結至pressure transducer 用以監視海綿體內壓力變化。將不同劑量的YC-1,papaverine,及 prostaglandin E1 注入白兔陰莖海綿體內後,監視其海綿體內壓力變化以得到 劑量-反應曲線。再於先施以低劑量的YC-1 20 分鐘後,再次求得papaverine, 及prostaglandin E1 的劑量-反應曲線,並與先前結果相比較。實驗中將持續對 白兔的血壓變化進行監視。 結果:一)海綿體內YC-1 注射會使白兔陰莖海綿體內壓力發生dose-dependent 方式的上昇,然其上昇效果並不顯著。二)海綿體內PGE1 注射同樣會使白兔陰 莖海綿體內壓力發生dose-dependent 方式的上昇,而其上昇效果也是並不顯 4 著。在少量YC-1 的存在下,其上昇效果會被增強。。三)海綿體內papaverine 注射會使白兔陰莖海綿體內壓力發生dose-dependent 方式的明顯上昇,其最大 反應壓力高過血管收縮壓而使白兔陰莖產生堅硬的勃起。 結論:YC-1 這種國內新合成的藥物注射入白兔陰莖海綿體時,會使陰莖海綿體 內壓力上昇而發生陰莖膨脹的現象。該藥物也會加強papaverine 引發白兔陰莖 勃起的效果。因此本實驗更進一步証實其可能用以治療男性勃起功能障礙的潛 力。 |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/25500 | 其他識別: | 892314B002299 | Rights: | 國立臺灣大學醫學院泌尿科 |
顯示於: | 醫學系 |
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